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BioE PhD Proposal- Jihoon Lee

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Advisor: 

Shuichi Takayama, Ph.D.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory School of Medicine

 

  

Committee Members:  

  

Stanislav Emelianov, Ph.D.

School of Electrical and Computer Engineering, Georgia Institute of Technology

 

M. G. Finn, Ph.D.

School of Chemistry and Biochemistry, Georgia Institute of Technology

 

Eric Sorscher, M.D.

Department of Pediatrics, Emory School of Medicine

 

Jason Spence, Ph.D.

Department of Cell and Developmental Biology, University of Michigan Medical School

 

Krishnendu Roy, Ph.D.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory School of Medicine

 

 

Human airway organoids with reversed biopolarity for high-throughput anti-SARS-CoV-2 Compound Screening 

 

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), has resulted in 6.5 million deaths worldwide since its emergence (as of 09/16/2022). Although slowed down in its pace thanks to the scientific advances achieved over the past two years, the virus remains a considerable threat. In a pressing demand for a rapid and efficient research tool for the ongoing pandemic, organoids have provided timely and powerful in vitro models to study viral tropism, host immune response, drug screening, and vaccine development. However, despite the immense number of research outputs, there have been varying and inconsistent results on host responses and pharmacodynamics, even within the same type of organoids. The observed variability may be attributed to challenging apical access in the conventional organoids, wherein the apical surface is sequestered away (“apical-in”) from the surrounding environment. Therefore, apical access is highly implicated, as it is the apical surface where the host-virus interactions predominantly occur. Our lab has recently demonstrated a high-throughput culture method of reproducible and uniform geometrically-inverted mammary epithelial organoids, in which the apical surface is stably oriented toward the organoid exterior (apical-out). The goal of the proposal is to adapt this method to human primary airway cells and utilise the resulting apical-out organoids as a high-throughput anti-SARS-CoV-2 compound screening platform. In Aim I, we will establish and optimise a culture of human bronchial epithelial organoids with reversed biopolarity (hBORBs). In Aim II, we will test and validate hBORBs as a high-throughput anti-SARS-CoV-2 compound screening platform. In Aim III, we will adapt the developed protocol to generate human nasal epithelial organoids with reversed biopolarity (hNORBs) derived from freshly isolated nasal epithelial cells.  

Status

  • Workflow Status:Published
  • Created By:Laura Paige
  • Created:09/20/2022
  • Modified By:Laura Paige
  • Modified:09/20/2022

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